Aluminum complexes nitriles

The mechanism for both of these reactions is very similar to the mechanism for the reduction of acyl chlorides by LATB—H. The first step is an acid-base reaction between an unshared electron pair on oxygen or nitrogen with the aluminum atom of the DIBAL—H. The second step is the transfer of a hydride ion from the DIBAL—H to the carbon atom of the carbonyl or nitrile group. The last step is the hydrolysis of the aluminum complex to form the aldehyde. 

Aluminum hydrides can reduce nitriles to the corresponding aldehydes. Diisobutylaluminum hydride, abbreviated (i-Bu AlH or DIBAL-H, is commonly used for the reduction of nitriles. The initial reaction forms an aluminum complex that hydrolyzes in the aqueous workup. 

Malonate and related activated methylene compounds have also been used as the nucleophile in conjugate addition/Michael reactions. Taylor and co-workers have developed a new methodology that utilizes (salen)aluminum complexes such as 43 as a catalyst to effect the enantioselective conjugate addition to a,p-unsaturated ketones by a variety of nucleophiles.25 For example, nitriles, nitroalkanes, hydrazoic acids, and azides have found utility in this reaction. Additionally, cyanoacetate (42) has been demonstrated to undergo a highly enantioselective conjugate addition to 41. The Krapcho decarboxylation is then necessary to produce cyanoketone 44, an intermediate in the synthesis of enantioenriched 2,4-cw-di substituted piperidine 45. 

Diisobutylaluminum hydride (DIBAL) is known to be less reactive than LiAUL and can transfer only one hydride ion per molecule. For this reason DIBAL is commonly used for partial reduction of esters and nitriles. Addition of DIBAL to a nitrile results in the formation of an imine-aluminum complex that is decomposed, during workup, to the aldehyde (Scheme 14). Cyanohydrins have to be protected during the synthesis of a-hydroxy aldehydes because dimerization and isomerization can take place. Even in the protected form special care has to be taken during synthesis (low temperatures) and workup [124,136]. 

The reaction of sulfur dichloride with benzonitrile in the presence of a Lewis acid catalyst yields 3,5-diphenyl-l,2,4-thiadiazole (39), along with the 3-o-chlorophenyl (278) and 3-p-chlorophenyl (279) analogues in a total yield of 80%. The proposed mechanism proceeds via a complex between benzonitrile, Lewis acid for example, aluminum trichloride, and sulfur dichloride to give an intermediate (280) which then adds a second molecule of nitrile (Scheme 62) <83BCJ180>. 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

As with aluminum, most recent work on nitrile complexes has been directed to understanding the constitution of solutions of GaX3 in MeCN. NMR measurements have been... 

Intramolecular acylation has been used frequently. Houben-Hoesch cyclization of 1 -/ -cyanoethylpyrrole (2a) gives l-oxo-2,3-dihydropyrrolizine (3a).9-17 Difficulties occur because polymerization of the nitrile (2a) can be a side reaction. Addition of boron trifluoride [3a (33%)]11 or its ethyl ether complex [3a (60-80%)]15 has been recommended. Treatment of nitrile 2a with a molten aluminum chloride-potassium chloride-sodium chloride mixture yields 70% of ketone 3a but the experimental conditions are highly critical.13 A reproducible procedure that is based mainly on Clemo s specification9,10 gave 22% of ketone 3a.17 Purification of 3a should be carried out in an efficient fume hood because it appears to induce analgesia.1 ... 

T he free radical initiated polymerization of polar monomers containing pendant nitrile and carbonyl groups—e.g., acrylonitrile and methyl methacrylate—in the presence of metal halides such as zinc chloride and aluminum chloride, is characterized by increased rates of polymerization (2, 3, 4, 5,10, 30, 31, 32, 33, 34, 53, 55, 65, 66, 75, 76, 77, 87). Imoto and Otsu (30, 33, 34) have attributed this effect to the formation of a complex between the polar group and the metal halide. The enhanced reactivity of the complexed monomer extends to copolymerization with uncomplexed monomers, such as vinylidene chloride, which are readily responsive to... 

The complex of a cyclobutadiene with aluminum chloride reacted with nitriles to give pyridine derivatives, where the intermediates must be Dewar pyridines (Eq. 32).97... 

The rate of polymerization of polar monomers, for example, maleic anhydride, acrylonitrile, or methyl methacrylate, can be enhanced by coraplexing them with a metal halide (zinc or vanadium chloride) or an organoaluminum halide (ethyl aluminum sesqui-chloride). These complexed monomers participate in a one-electron transfer reaction with either an uncomplexed monomer or another electron-donor monomer, for example, olefin, diene, or styrene, and thus form alternating copolymers (11) with free-radical initiators. An alternating styrene/acrylonitrile copolymer (12) has been prepared by free-radical initiation of equimolar mixtures of the monomers in the presence of nitrile-coraplexing agents such as aluminum alkyls. 

At elevated temperatures 2 moles of dialkyl alane react with nitriles up to the amine stage. The dialkyl-dialkylamino alanes, R NR fCHaR"), resulting from azomethines form molecular compounds with strong donors. These are colored if the donor is an azomethine or an aromatic N heterocycle and may be used for the quantitative determination of A1H groups in organic aluminum compounds 191). Complex salts such as Li[(RO)jAlH] 37, 38) or Na iC s AlIR] 287) may be used in the preparation of aldehydes instead of diisobutylalane (cf. Section V,D,3b). 

Enantiopure sulfinimines (thiooxime-S-oxides) 44 have been reported to facilitate the asymmetric Strecker reaction.28 Davis found that typical cyanide sources, such as potassium cyanide and TMSCN, did not possess sufficient reactivity for addition to the sulfinimines. Product 46, however, could be obtained using the more Lewis acidic Et2AlCN. Not only did the coordination of the aluminum to the oxygen of the sulfinimine activate the imine toward nucleophilic addition, this complexation also facilitated the delivery of the nitrile (see 45), These results triggered numerous modifications and variations that have enhanced this approach to chiral a-amino acids. 

The paper reports preparation of two new copper hydride complexes. The lithium complex (1) is prepared from CuBr and 2 equiv. of lithium trimethoxy-aluminum hydride (cf. 5, 168) the sodium complex (2) is prepared from CuBr and 1 equiv. of sodium bis(2-methoxyethoxy)aluminum hydride. Both complexes are useful for selective reduction of the double bond of conjugated cnones 1 is more efficient for reduction of cyclohexenones and 2 is more efficient for reduction of acyclic enones. Aldehydes, ketones, and halides are also reduced nitrile and ester units are inert. The effective stoichiometry of both reagents is consistent with the structures LiCuHj and NaCuHs, but complex 1 is clearly different from a reagent assigned the structure LiCuHa by Ashby et al. ... 

The problem is apparently due to some residual aluminum that is hard to remove. If, however, the reduction is carried out in a iV-methylmorpholine solution, followed by addition of potassium tartrate, a pure product can be isolated. A -Methylmorpholine is a good solvent for reductions of various macromolecules with metal hydrides.In addition, the solvent permits the use of strong NaOH solutions to hydrolyze the addition complexes that form. Other polymers that can be reduced in it are those bearing nitrile, amide, imide, lactam, and oxime pendant groups. Reduction of polymethacrylonitrile, however, yields a product with only 70% of primary amine groups. Complete reductions of pendant carbonyl groups with LiAlH4 in solvents other than A -methyl-morpholine, however, were reported. Thus, a copolymer of methyl vinyl ketone with styrene was fully reduced in tetrahydrofuran. ... 

Thus, Styrene can be more easily induced to polymerize than vinyl acetate. In reverse, the poly(vinyl acetate) free radical is about 1000 times more reactive than the poly(styrene) free radical. In general, monomers more easily activated to polymerize give more stable free radicals, and vice versa. In these cases, the reactivity can, as expected, be influenced by complexation of the substituents, for example, with Lewis acids such as zinc chloride, or aluminum chloride in the case of nitrile or carboxy group containing monomers. 

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